WCLC 2025 - Posters & ePosters-EP.06.04 Extranodal Extension in Lung Adenocarcinoma: Pathological Insights and Its Role as an Independent Prognostic Factor

EP.06.04 Extranodal Extension in Lung Adenocarcinoma: Pathological Insights and Its Role as an Independent Prognostic Factor

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This study investigates extranodal extension (ENE) in lung adenocarcinoma, focusing on its pathological characteristics and prognostic significance. ENE, the spread of cancer beyond the lymph node capsule into surrounding tissue, is recognized as a key factor in various cancers, but its role in lung adenocarcinoma needed clarification.<br /><br />The researchers retrospectively analyzed 105 patients with N1 or N2 lung adenocarcinoma who underwent lung resection from 2016 to 2020. Using artificial intelligence-based image analysis, they quantified tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), cancer cells, and fibrous stroma in primary tumors and metastatic lymph nodes. An in vitro invasion assay tested the impact of CAF abundance on cancer cell invasiveness.<br /><br />Findings revealed no significant difference in immune cell populations or fibrous stroma within primary tumors between ENE-positive and ENE-negative patients. However, metastatic lymph nodes with ENE exhibited significantly greater fibrous stroma areas (14.2 mm² vs. 4.0 mm²; p<0.001). In vitro, co-culture with increased CAFs significantly enhanced the invasiveness of A549 lung cancer cells, suggesting a role of CAF-rich microenvironments in cancer progression.<br /><br />Clinically, ENE emerged as an independent poor prognostic factor for overall survival (p=0.04) and was significantly linked to higher risk of distant metastasis (multivariate p=0.03, cumulative incidence p=0.02). Pathological features indicate that ENE-positive nodes have abundant fibrous stroma, reflecting a tumor microenvironment conducive to aggressive behavior.<br /><br />In conclusion, ENE is a strong pathological and prognostic marker in lung adenocarcinoma, associated with worsened survival and distant recurrence. Its detection and quantification may improve N staging accuracy and help guide postoperative management. The study underscores the role of the tumor microenvironment, particularly CAFs and fibrous stroma, in facilitating ENE and metastatic progression.

Asset Subtitle

shunta tsuchida

Meta Tag

Speaker shunta tsuchida

Topic Pathology and Biomarkers

Keywords

extranodal extension

lung adenocarcinoma

tumor microenvironment

cancer-associated fibroblasts

fibrous stroma

tumor-infiltrating lymphocytes

tumor-associated macrophages

N staging

prognostic marker

metastatic lymph nodes